Umbilical Threonine Uptake during Maternal Threonine Infusion in Sheep

Abstract

Objective: The infusion into the maternal circulation of amino acid solutions failed to increase umbilical threonine (THR) uptake above normal even when THR was present in the infusate at a relatively high concentration. The purpose of the present study was to determine whether umbilical THR uptake can be increased by infusing a THR solution that does not contain any other amino acids.Study design: Five pregnant sheep (130±1.0 days after conception) were infused for 2h with a threonine solution (4.4±0.2μmol·kg−1·min−1). Plasma amino acids, glucose and lactate, hematocrit, blood O2 content in maternal arterial, uterine venous, umbilical arterial and venous blood were measured. Uterine and umbilical blood flows were measured before and during the infusion and were used to calculate uterine and umbilical uptakes. Maternal and foetal plasma insulin and glucagon concentrations were also measured.Results: The THR infusion increased maternal plasma THR (904 vs 236μm , P< 0.001), foetal plasma THR (539 vs 334μm , P< 0.01), and both uterine (20.4 vs 4.7μmol·min−1·kg−1fetalweight, P< 0.05) and umbilical (8.6 vs 3.8μmol·min−1·kg−1fetalweight, P< 0.001) THR uptakes. The uterine-umbilical THR uptake difference increased significantly (11.8 vs 0.9μmol·min−1·kg−1fetalweight, P< 0.05). There were significant (P< 0.001) decreases in the foetal arterial plasma concentrations of tyrosine and the branched chain amino acids, as well as in isoleucine umbilical uptake (P< 0.05). There was a significant increase in maternal plasma glucagon (P< 0.01).Conclusion: A maternal THR infusion that causes a 3.8-fold increase in maternal plasma THR concentration above normal, with no significant increase in the concentration of other amino acids, leads to a 2.3-fold increase in umbilical THR uptake. This contrasts with the absence of a significant increase in umbilical THR uptake when THR was infused as part of an amino acid mixture in previous studies. The evidence supports the hypothesis that, in vivo, THR flux from placenta to foetus is mediated by a saturable, rate limiting transport system which is subject to inhibition by other neutral amino acids.